Scandinavian Journal of Surgery 98: 225–228, 2009
SUB-LOBAR LUNG RESECTION OF PERIPHERAL T1N0M0 NSCLC DOES NOT AFFECT LOCAL RECURRENCE RATE T. De Giacomo, M. Di Stasio, D. Diso, M. Anile, F. Venuta, G. Furio Coloni University of Rome “Sapienza”, Department of Thoracic Surgery, Policlinico Umberto I, Rome, Italy
ABSTRACT
Background and Aims: The use of sub-lobar resection versus lobectomy for stage I non small cell lung cancer is still controversial. This study was undertaken to compare the results of limited resection in terms of survival and local recurrence rate to lobectomy in patients with peripheral stage I non small cell lung cancer. Material and Methods: During the 8 year period from 1999 to 2007, 152 consecutive patients with stage I non-small cell lung cancer underwent lung resection at our thoracic surgery unit. In 116 cases we performed a standard lobectomy while in the remaining 36 cases we did sub lobar resection through mini-thoracotomy or video-assisted thoracoscopy. The survival, local recurrence rate and the clinical outcome were analyzed and compared. Results: Fifty-one patients were staged as T1 N0 M0, 22 in the sub-lobar resection group (61,1%) and 29 (25%) in the lobectomy group. The remaining were staged as T2 N0 M0. Although the patient population undergone to sub-lobar resection was older, with poorer lung function and more co-morbidities, the Kaplan-Meier survival proportion at 5 year did not differ significantly between the two groups: 64% for lobectomy group vs 66,7% for sub-lobar resection group. Overall local recurrence did approach significance in favour of lobectomy group but analyzing only T1 patients, no differences in terms of survival and local recurrence rate were observed. Conclusions: The results of this study indicate that in patients with peripheral T1N0M0 non small cell lung cancer the outcome of limited resection is comparable with that of pulmonary lobectomy. Key words: Lung cancer; wedge resection; segmentectomy; stage I ; VATS; lobectomy
InTRODUCTIOn The use of sub-lobar lung resection as definitive management of resectable non small cell lung cancer (nSCLC) is a controversial issue. In 1995 the Lung Cancer Study Group (LCSG) in the one and only ranCorrespondence: Tiziano De Giacomo M.D. University of Rome “Sapienza” Thoracic Surgery, Policlinico “Umberto I” V.le Policlinico 155 00161 Rome, Italy Email:
[email protected]
domized trial comparing sub-lobar to lobar resection (1) demonstrated a 3-fold increase in the local recurrence rate among patients who underwent sub-lobar resection. Other non-randomized trials comparing sub-lobar resection to lobectomy (2) demonstrated a trend for increased local recurrence. As result of these studies, most thoracic surgeons consider pulmonary resection less than lobectomy inadequate for the management of lung cancer. The use of high resolution computed tomography (CT) and the widespread practice of low dose helical CT for lung cancer screening has led to the identification of an increasing number of T1 cancer, and with this, reconsideration on the use of sub-lobar resections. Several reports demon-
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strated that sub-lobar resection was not inferior to lobectomy regarding the prognosis of patients with small and peripheral nSCLC (3–4). Removing a relatively large areas of healthy lung tissue may result in an increased operative morbidity, poorer post-operative quality of life and reduced chance for further resection. As for other kind of surgery, like in breast cancer, there may be a favourable group of patients who could benefit of limited resection without affecting the oncologic outcome. The rigid consensus on lobectomy for stage I cancer, has made difficult to carry out a randomized study. We report this retrospective study comparing sub-lobar resection with lobectomy in patients with peripheral stage I nSCLC. MATERIAL AnD METhODS From January 1994 to December 2000 we have treated 152 patients with stage I peripheral nSCLC. They had no history of previously treated cancer. Pre-operative study included careful history and physical examination, fiberbronchoscopy, full pulmonary function analyses with blood gas determination, standard chest X-ray film and whole body CT scan. no further metastatic workup was performed routinely but other studies (bone scintigraphy, brain and abdomen MRI) were used selectively to investigate specific preoperative symptoms potentially related to metastatic disease. One hundred and sixteen patients underwent anatomic lobectomy. All sublobar resections were approached with VATS technique. In 14 cases (39%), because of the presence of strong adhensions between lung and chest wall, we converted the procedure in a limited lateral thoracotomy measuring less than 8 cm in length. We performed 28 non-anatomical wedge resections (78%) and 8 segmentectomies (22%). The decision to use sub-lobar resection was related to the patient’s physiologic condition
precluding lobar resection. The age and the degree of underlying pulmonary disability are noted in Table 1. Mediastinal and hilar lymph node staging was routinely performed during the surgical procedure of all patients, while radical mediastinal lymph node dissection was not performed in the VATS group. Resected specimens were examined by the same pathologist and histologic typing was done according to the World health Organization classification (5). Surgical-pathologic staging was performed according to the new International Staging System of Lung cancer (6). The vast majority of patients undergoing open thoracotomy for lobectomy or wedge resection were managed with epidural analgesic measures during the early postoperative period. Post-operative care was similar between lobectomy and sub-lobar resection. The median length of documented follow-up was 59 months. Local recurrence was defined as any recurrence of the primary cancer in the hemithorax. Systemic disease was defined as the presence of metastatic disease without local recurrence within the ipsilateral hemithorax. Local and systemic disease was defined as the association of local recurrence and new roentgenographic, scintigraphic or histologic evidence of distant metastases. Survival was estimated by the Kaplan- Meier method (7) and differences in survival were determined by log-rank analysis. Multivariate analysis with prognostic stratification variables was done using Cox proportional hazards regression model (8).
RESULTS Two patients died after lobectomy in the post-operative period for myocardial infarction. none died in the sub-lobar resection group. Length of hospital stay, chest drainage duration and complications (mostly, prolonged air leaks and atrial fibrillation) are reported in Table 2.
TAbLE 1 Characteristics of patients of the two groups. Lobectomy 116 patients Male Female Age FEV1 Comorbidities T1 nO M0 Adenocarcinoma Squamous cell bronchoalveolar Indifferentiated
99 (85%) 17 (15%) 64,8 ± 8,7 84,9% ± 18,5 57 (49%) 29 (25%) 50 (43,1%) 45 (38,8%) 10 (8,6%) 11 (9,5%)
Sub-lobar resection 36 patients
pValue
31 (86%) 5 (14%) 68,7±8,4 71% ± 25,6 26 (72%) 22 (61%) 13 (36,1%) 10 (27,8%) 10 (27,8%) 3 (8,3%)
0,57 0,56 0,01 0,01 0,02 0,004 0,58 0,32 0,007 0,9
TAbLE 2 Perioperative data and complications of the two groups.
Mean hospital stay Mean chest tube duration Death Complications
Lobectomy
Sub-lobar resection
p Value
10 ± 5,3 days 8 ± 4,9 days 2 34 (29,3%)
5 ± 3,4 days 4 ± 2,5 days 0 8 (22,2%)
0,001 0,003 0,9 0,8
Sublobar resection for stage I NSCLC
DISCUSSIOn To advocate limited resection for treating stage I nSCLC, there must be some clinically significant advantage when compared with lobectomy. Increased residual pulmonary function, lower morbidity and
Cumulative Proportion Surviving
Survival by groups
Months
Lobectomies Sublobar resections
Fig.1. Kaplan-Meier survival proportion at 5 year between the two groups: 64,4% for the lobectomy group vs 66,7% for the sub-lobar resection group (log-rank test, p = 0,3).
Survival by Stage IA
Cumulative Proportion Surviving
Fifty-one patients were staged as T1n0M0: 22 (61,1%) in the sub-lobar resection group and 29 (25%) in the lobectomy group and this difference resulted statistically significant (p = 0,004). The remaining were staged as T2n0M0. Analysis of the distribution of histological types between the two groups showed that broncho-alveolar carcinoma was statistically significant more frequent in the sub-lobar resection group (Table 2). The median diameter of lesions resected by lobectomy was 2,3 cm, larger than the group managed with sub-lobar resection (1,8 cm.) but this difference did not reach statistical significance. The primary oncologic end-points of this study were the long term survival and the relative risk for local and distant recurrence after either sub-lobar resection or lobectomy. Although the patient population undergone to sub-lobar resection was generally older, with poorer lung function and more co-morbidities, the Kaplan-Meier survival proportion at 5 year did not differ significantly between the two groups: 64,4% for the lobectomy group vs 66,7% for the sub-lobar resection group (log-rank test, p = 0,3) (Fig. 1). Local recurrence did approach significance in favour of lobectomy group: it was identified in 8 patients of the lobectomy group (6,9%) and 9 patients in the sublobar resection group (25%) (p < 0,0006). however, in the latter group no statistically significant differences were observed between non-anatomical wedge resections and segmentectomies patients. Analyzing only the patients staged as T1, no differences in terms of survival and local recurrence were observed between the two groups. The Kaplan-Meier survival analysis at 5 year was as follow: 78,6% after lobectomy and 79,1% after sub-lobar resection (log rank p = 0,2) (Fig. 2). Local recurrence was observed in 2 patients after lobectomy (1,7%) and in 2 after sub-lobar resection (5,5%) (p = 0,8). Distant recurrence was similar in the two groups: 24% in the lobectomy group and 11% in the sub-lobar resection group (p = 0,14). Although the 5 year survival for patients staged as T2 n0 was comparable 59,7% after lobectomy and 65,4% after sub-lobar resection (log rank 0,18), the local recurrence rate was higher after sublobar resection (19,2%) than after lobectomy (5,1%) and the difference reached statistical significance (p = 0,001). Distant recurrence rate was similar between the two groups (24% after lobectomy 11% after sublobar resection p = 0,14). In addition, to control for the effect of other factors and to estimate risk ratio we used the Cox proportional hazard model including the following variables: sex, age, smoking, tumor size, FEV1, co-morbidities, type of resection complications and local recurrence. The only significant variables found to have impact on survival were age (p = 0,001 risk ratio = 3,59) and local recurrence (p = 0,01 risk ratio 2,4).
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Months
Lobectomies Sublobar resections
Fig. 2. Kaplan-Meier survival analysis at 5 year for stage IA patients: 78,6% after lobectomy and 79,1% after sub-lobar resection (log rank p = 0,2).
mortality have been reported (9–10). In particular, pre-operative pulmonary function may have significant influence on post-operative morbidity and mortality (11), suggesting that for patients with small and peripheral cancer and poor lung function, lobectomy should not be the preferred procedure. The large use of CT scan for lung cancer screening, has led to the identification of an increasing number of T1 tumors, and with this, reconsideration on the use of sub-lobar resection. T1 n0 tumors larger than 2 cm have an overall poor prognosis when compared to T1 n0 smaller than 2 cm. (12). Fernando and coll. (13) reported that in patients with IA nSCLC smaller than 2 cm. there was no difference in median survival between sub-lobar resection and lobectomy, whereas for lesions of 2 to 3 cm in size survival was significantly better after lobectomy. Other studies reported no difference in survival and in local recurrence rate be-
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tween limited resection and lobectomy in patients with stage I nSCLC smaller than 1 cm (14–15). These observations are evident also in our study: analyzing patients with stage IA, there was no difference in 5 year survival and local recurrence rate between lobectomy and limited resection. Furthermore, no differences were reported considering the histological subtypes. however, larger lesions had higher recurrence rate in the sub-lobar resection group than in the lobectomy group. Similar results were described by El-Sherif and colleagues (16). Local recurrence rate and age in our study were the only factors influencing survival. The development of local recurrence after a clear resection might represent a manifestation of an aggressive metastatic phenotype of the malignant tumor rather than a failure of the surgical therapy. Since 30–35% of patient with stage IA cancer, will relapse at some point, a subgroup of these patients may benefit from receiving chemotherapy in addition to surgery. however, existing clinical trials indicate no benefit in giving these patients chemotherapy. Distinguishing between patients with a high risk of early recurrence and those with a long disease-free interval following resection is topic of great interest and intense study. There is a growing literature supporting the use of genomics and proteomics to characterize lung cancer (17–18). Genetic and phenotypic analysis and prognostic molecular marker testing might play a determinant role in the development of individualized patient treatment, especially in early stage lung cancer. Although there is no statistically differences between lobectomy and limited resection in terms of complication and peri-operative mortality in our study, we have observed a shorter hospital stay and better recovery. Preserving lung parenchyma with sub-lobar resection can contribute to a lower occurrence of lung dysfunction, and post-operative morbidity and mortality. Okada clearly demonstrated that sublobar resection provided better preservation of FVC and FEV1 compared to lobar resection at 2 months after surgery (19). In conclusion, despite the non-randomized nature of our study, our results support the idea that sublobar resection with sufficient safe margins appears to be a viable surgical treatment of stage T1n0M0 peripheral non small cell lung cancer.
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Received: March 10, 2009 Accepted: August 27, 2009
